Neural progenitor cells (NPCs) derived from human embryonic stem cells (hESCs) have great potential in cell therapy, drug screening and toxicity testing of neural degenerative diseases. However, the molecular regulation of their proliferation and apoptosis, which needs to be revealed before clinical application, is largely unknown.
Researchers from the Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Shanghai Jiao Tong University School of Medicine, use hESC neural differentiation model to unveil the molecular mechanism underlying neurotoxin-induced apoptosis in NPCs.
A team of researchers led by stem cell biologist JIN Ying, director of CAS Key Laboratory of Stem Cell Biology, have successfully established several hESC lines with unlimited self-renewal and pluripotent ability and generated NPCs from two independent hESC lines. In this study, the researchers found a microRNA, miR-195, as a critical regulator in coordinating survival and apoptosis in NPCs and identified a GTP binding protein, ADP-ribosylation factor-like protein 2 (ARL2), as a functional downstream target of miR-195.
Furthermore, both miR-195 and ARL2 were regulated during apoptosis caused by treatment of neurotoxin, paraquat and rotenone, indicating the possible involvement of miR-195 in regulating neurotoxin-induced NPC apoptosis. Considering paraquat and rotenone as etiological factors in Parkinson’s disease, the related miR-195 might be helpful for understanding the pathogenesis of Parkinson’s disease, and provide new therapeutic targets.
This work entitled “MicroRNA-195 targets ADP-ribosylation factor-like protein 2 to induce apoptosis in human embryonic stem cell-derived neural progenitor cells” has been published in the journal Cell Death and Disease.
The study was supported by grants of the National Natural Science Foundation (91019023 and 30900858), National High Technology Research and Development Program of China (2010CB945200, 2011DFB300100, 2010CB965101 and 2009CB941103), Chinese Academy of Science (XDA01010102), Shanghai Leading Academic Discipline Project (S30201) and grants from Ministry of Education of China (20110073110082).
CONTACT:
JIN Ying
Key Laboratory of Stem Cell Biology, Institute of Health Sciences,
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine,
225 South Chongqing Road, Shanghai 200025, China.